The betaine-dependent remethylation pathway is a homocysteine metabolism pathway associated with the carnivorous feeding habits of spiders.

Homocysteine (Hcy) is a sulfur-containing amino acid derived from the essential amino acid methionine (Met). Circulating levels of Hcy in animals can be increased by feeding on Met-enriched diets, which is generally considered harmful. Spiders are one of the largest groups of obligate carnivores and feed on animals high in protein and Met. We analyzed the Hcy metabolism pathways in 18 species of 3 taxa (Mammalia, Insecta, and Arachnida) and found that the betaine-dependent remethylation pathway (BRP) was present in all carnivorous arachnid species and mammals but absent in insects and red spider mites. We then studied the Hcy metabolism pathway in Pardosa pseudoannulata. In P. pseudoannulata, Hcy is metabolized through the transsulfuration pathway, BRP, and S-methylmethionine-dependent remethylation pathway. Because of a prior duplication event of the betaine homocysteine S-methyltransferase (BHMT) gene in the BRP, BHMTa and BHMTb are present in tandem in the genome of P. pseudoannulata. The high expression levels of BHMTa and its high abundance in detoxification tissues indicate that it plays an important role in the BRP; the ability of BHMTa and BHMTb to remethylate Hcy using betaine as substrate was similar. Compared with other Hcy metabolic enzyme genes, BHMT responded quickly to the application of Hcy or betaine. In sum, the BRP is important in Hcy metabolism in P. pseudoannulata and in other spider species.